Management of chronic hepatitis B

Area of Science:

• Hepatology
• Virology
• Pharmacology

Background:

• Chronic hepatitis B (CHB) poses significant risks including death, hepatic decompensation, and hepatocellular carcinoma (HCC).
• Understanding the natural history of CHB and the efficacy/safety of antiviral therapies is crucial for patient management.

Purpose of the Study:

• To synthesize evidence on the natural history of CHB.
• To evaluate the effects and harms of antiviral drugs on clinical, virological, histological, and biochemical outcomes in adults with CHB.

Main Methods:

• Systematic review of observational studies for natural history and randomized controlled trials (RCTs) for treatment effects.
• Inclusion criteria focused on adults with CHB, specific outcome measures (mortality, HCC, cirrhosis, viral load, ALT, histology, adverse events), and specific antiviral agents.
• Exclusion criteria included pregnant women, transplant patients, and those undergoing chemotherapy.

Main Results:

• Observational data linked male gender, coinfection (HCV, HDV, HIV), high HBV DNA, and cirrhosis to increased HCC and mortality risk.
• Antiviral drugs did not demonstrate reduction in death, liver failure, or HCC in RCTs not designed for long-term outcomes.
• Evidence from 60 RCTs showed treatments improved viral load, liver enzymes, and histology, with effects lasting 3-6 months post-treatment; no single treatment improved all outcomes.
• Specific agents like interferon alfa-2b, lamivudine, adefovir, and pegylated interferon alfa 2-a showed varied improvements in virological and biochemical markers, with some combination therapies offering additional benefits.
• Adverse events were common but generally mild, not leading to increased discontinuation.
• Factors like hepatitis duration, male gender, baseline viral load, genotype, HBeAg status, and histology may modify treatment effects on intermediate outcomes.
• Adefovir and pegylated interferon alfa 2-a with lamivudine showed improved off-treatment viral clearance in HBeAg-negative patients.
• Insufficient evidence exists to validate intermediate measures (biochemical, viral, histological) as surrogates for long-term clinical outcomes.

Conclusions:

• Adults with CHB face elevated risks of mortality, hepatic decompensation, and HCC.
• Current antiviral therapies (mono or combined) improve select virological, biochemical, and histological markers but lack consistent effects across all outcomes.
• Patient and disease characteristics can influence treatment-induced intermediate outcomes.
• Evidence is insufficient to assess treatment impact on clinical outcomes, predict individual responses, or confirm the reliability of intermediate measures as surrogates.
• Future research should focus on long-term drug effects on clinical outcomes and specific patient subpopulations.